A. Field of the Invention
The present invention relates generally to the fields of immunology and disease therapy. More particularly, it concerns the use of insect cell compositions as adjuvants to promote antigen specific immunological responses.
B. Description of Related Art
Methods for manipulating the immune system to achieve a desired effect have been known for many years, and are used both in the prevention and therapy of disease and in immunization protocols to generate specific antibodies for other uses, e.g., in diagnostics. However, generating an appropriate immune response is not always a straightforward matter. Particular problems arise with antigens that are “immunologically cryptic,” in which cases the immune responses are often too weak to be of practical use.
The problems associated with generating immune responses apply to a wide range of clinical and laboratory protocols, with one of the most important areas being that of cancer treatment and therapy. Various modalities of therapy have been used during the past 30 years to treat cancer, including radiation and chemotherapy, radical surgery and immunologically-based protocols. Nevertheless, despite improvements in early diagnosis, surgical techniques and local and systemic therapies, most deaths from cancer result from metastases that are resistant to conventional therapies. Because systemic spread occurs early in the growth of many malignancies, surgery and radiotherapy may fail to achieve cure despite thorough eradication of the local disease. Chemotherapy is potent and systemic in its effects, but kills tumor cells by first-order kinetics so the last cancer cell may not be eliminated (Fidler, 1999). The goal of anti-cancer immunotherapy is the recruitment of the host immune system to destroy not only the primary neoplasm, but also any secondary metastatic cells. Cancer vaccines are mostly used for this purpose and are dependent on the presence of tumor-specific antigens and the ability to induce a cytotoxic immune response that recognizes tumor cells presenting antigens.
Tumor-associated antigens (TAAs) capable of being recognized by the cellular immune system (T-cells) have been identified. These antigens (also referred to as tumor associated or T-cell epitopes) include oncogene products activated by mutation and rearrangement (e.g., position 12 mutation in p21ras; P210 product of bcr/abl rearrangement); mutated tumor-suppressor gene products (e.g., p53); reactivated embryonic gene products not expressed in adult tissues (e.g., P91A found in the P815 mastocytoma); MAGE 1 (found in melanomas and human breast tumors); tissue specific self-antigens expressed by tumors (e.g., tyrosinase); and a variety of others (Pardoll, 1993). Most tumor cell populations express certain common TAAs, but are heterogeneous with respect to the spectrum of TAAs that they express. Despite the array of tumor-associated T-cell epitopes expressed in tumors, tumor cells remain poorly immunogenic.
Thus, a major hurdle faced in the use of cancer vaccines is that many tumors, though potentially immunogenic, do not stimulate an effective antitumor immune response (Mueller, 1989). Most progressively growing neoplasms do not provoke immunological responses sufficient to control the growth of malignant cells, despite the fact that tumor cells express antigens which are recognizable as foreign by the immune system of the patient (Sibille et al., 1990).
Despite the continuing efforts in this field, it is apparent that improved methods and novel strategies for generating immune responses are still needed. Simple methods that are appropriate for use with a wide variety of antigens are particularly desirable. The development of a method by which to improve the immune response against immunologically cryptic antigens would represent a significant advance, particularly if such a method was adaptable for use against clinically relevant antigens.